This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dengue is the second most important tropical disease after malaria, with 50[unreadable]100 million cases of Dengue Fever (DF) and 500,000 cases of Dengue Hemorrhagic Fever (DHF) each year. DHF is a severe life threatening complication resulting from wide spread vascular damage and hypertensive shock. To date efforts to develop a vaccine have not been effective. The goal of immunization is to protect against dengue virus (DV) disease by inducing a long-lived neutralizing antibody response against each of the four serotypes. Simultaneous protection against all four serotypes is required, since an increase in disease severity can occur in persons with preexisting antibodies to a heterotypic DV. Conventional and recombinant strategies have been followed to develop a dengue vaccine. Despite the urgent need for a vaccine, basic questions remain concerning the correlates of protection and the role of immune responses in producing DHF. Previous work has suggested a role for antibody enhancement of viral replication and in appropriate T cell responses in the pathogenesis of DHF. Development of a vaccine is hampered over concerns that elicited immune responses may exacerbate disease in a subset of poorly protected patients.